Antibodies to nucleic acids are important diagnostically and pathogenically in systemic lupus. The production of these antibodies is in part controlled by the X-chromosome through regulation of maturation of beta cells destined to make IgM antibodies to nucleic acids. Sex chromosomes indirectly influence the magnitude to auto-antibody production through sex hormones: male sex hormones suppress the production of anti-nucleic acid antibodies. Antibodies to transfer RNA are produced by patients with SLE; these crossreact with viral nucleic acids. Subpopulations of patients have specific auto-antibodies. Hybridoma cells producing anti-nucleic antibodies (derived originally by fusing BALB/c and NZB times NZW F1 cells) preferentially grow and preferentially produce different antoantibodies in different recipient strains. These studies suggest that control mechanisms exist for the proliferation of, and perhaps synthesis by, B cells genetically destined to produce antibodies to nucleic acids.